This is a pilot study designed to apply neuroimaging techniques, not previously used in the sickle cell population, in an effort to document subcortical, as well as cortical, changes in perfusion and how these changes correlate with neuropsychological test performance. This pilot will provide us with the statistical parameters necessary to determine an adequate sample size needed to specify the factors contributing to neuropsychological impairment seen in children with Sickle Cell Disease (SCD) who have no evidence of cerebral infarction on conventional Magnetic Resonance Imaging (MRI). Such a larger study will ultimately enable us to determine an optimum threshold for clinical intervention in an effort to avoid progressive cognitive deterioration. This proposed study will: (1) examine the relationship between proximal and distal parenchymal perfusion to test the hypothesis that as cerebral blood flow velocity in the individual major cerebral arteries increases, perfusion at the arteriolar/capillary level will decrease; (2) examine the relationship between proximal and distal parenchymal perfusion and neuropsychological test performance scores at baseline to test the hypothesis that (a) the combined use of perfusion MR imaging and transcranial Doppler (TCD) will provide additional information about the extent of cerebral physiological dysfunction and how it correlates with neuropsychological test performance and (b) that there is a relationship between changes in perfusion in specific regional areas and performance on specific neuropsychological domains at baseline; and (3) monitor changes in perfusion and neuropsychological performance at 6 and 12 months to test the hypothesis that changes in perfusion over time will be associated with changes in neuropsychological test performance. To test these hypotheses, this study will assess: (a) neuropsychological test performance, (b) distal parenchymal perfusion via perfusion MR imaging; (c) flow velocity in the large proximal intracerebral arteries via transcranial Doppler (TCD) and flow quantitative phase-contrast MRA, and (d) anatomical MR imaging, in a prospective, longitudinal study semi- annually. We anticipate that findings from the proposed plan will enhance knowledge of the neurodevelopmental consequences of SCD, provide information for purposes of stroke screening and managing therapeutic treatment regimens, and generate new information on the clinical utility of MR perfusion imaging in identifying global and/or regional ischemia. The latter in combination with TCD studies will also elucidate the relationship between proximal characteristics observed by TCD and true end organ perfusion outlined by MR.